tbuckley/cabot-search huggingface dataset:
<i>TP53</i>-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia: Biology, Current Therapy, and Future Directions
Authors: Naval G. Daver, Abhishek Maiti, Tapan M. Kadia, Paresh Vyas, Ravindra Majeti, Andrew H. Wei, Guillermo Garcia-Manero, Charles Craddock, David A. Sallman, Hagop M. Kantarjian
Journal: Cancer Discovery (2022)

TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) form a distinct group of myeloid disorders with dismal outcomes. TP53-mutated MDS and AML have lower response rates to either induction chemotherapy, hypomethylating agent-based regimens, or venetoclax-based therapies compared with non-TP53-mutated counterparts and a poor median overall survival of 5 to 10 months. Recent advances have identified novel pathogenic mechanisms in TP53-mutated myeloid malignancies, which have the potential to improve treatment strategies in this distinct clinical subgroup. In this review, we discuss recent insights into the biology of TP53-mutated MDS/AML, current treatments, and emerging therapies, including immunotherapeutic and nonimmune-based approaches for this entity. Emerging data on the impact of cytogenetic aberrations, TP53 allelic burden, immunobiology, and tumor microenvironment of TP53-mutated MDS and AML are further unraveling the complexity of this disease. An improved understanding of the functional consequences of TP53 mutations and immune dysregulation in TP53-mutated AML/MDS coupled with dismal outcomes has resulted in a shift from the use of cytotoxic and hypomethylating agent-based therapies to novel immune and nonimmune strategies for the treatment of this entity. It is hoped that these novel, rationally designed combinations will improve outcomes in this area of significant unmet need.
Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading
Authors: Nimansha Jain, Caroline A. Lewis, Jason D. Ulrich, David M. Holtzman
Journal: The Journal of Experimental Medicine (2022)

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD. Since genetically decreasing TREM2 function increases Aβ-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading. Using a mouse model of amyloidosis in which AD-tau is injected into the brain to induce Aβ-dependent tau seeding/spreading, we found that chronic administration of an activating TREM2 antibody increases peri-plaque microglial activation but surprisingly increases peri-plaque NP-tau pathology and neuritic dystrophy, without altering Aβ plaque burden. Our data suggest that sustained microglial activation through TREM2 that does not result in strong amyloid removal may exacerbate Aβ-induced tau pathology, which may have important clinical implications.
Analysis of Spectral Estimation Algorithms for Accurate Heart Rate and Respiration Rate Estimation Using an Ultra-Wideband Radar Sensor
Authors: Kareeb Hasan, Malikeh P. Ebrahim, Hongqiang Xu, Mehmet R. Yuce
Journal: IEEE Reviews in Biomedical Engineering (2022)

Non-contact vital sign monitoring has been an important research topic recently due to the ability to monitor patients for an extended period especially during sleep without requiring uncomfortable attachments. Radar is a popular sensor for vital sign monitoring research. Various algorithms have been proposed for estimating respiration rate and heart rate from the radar data. But many algorithms rely on Fast Fourier Transform (FFT) to convert time domain signal to the frequency domain and estimate vital signs, despite FFT having limitation of frequency resolution being inverse of the time interval of data sample. However, there are other spectral estimation algorithms, which have not been much researched into the suitability of vital sign estimation using radar signals. In this paper, we compared eight different types of spectral estimation algorithms, including FFT, for respiration rate and heart rate estimation of stationary subjects in a controlled environment. The evaluation is based on extensive data consisting of different stationary subject positions. Considering the results, the eligibility of algorithms other than FFT for respiration rate and heart rate estimation is demonstrated. Using this work, researchers can get an overview on which algorithm is suitable for their work without the need to review individual algorithms separately.
Preparation of particle-attached microneedles using a dry coating process
Authors: Jeong-Eun Choi, Hye-Ran Cha, Suwan Kim, Ji Seok Kim, Mun-Jin Kim, Hyeon Woo Chung, Seung-Ki Baek, Jae Myun Lee, Jung-Hwan Park
Journal: Journal of Controlled Release (2022)
Epigenetic regulation of B cells and its role in autoimmune pathogenesis
Authors: Fan Xiao, Ke Rui, Xiaofei Shi, Haijing Wu, Xiaoyan Cai, Kathy O. Lui, Qianjin Lu, Esteban Ballestar, Jie Tian, Hejian Zou, Liwei Lu
Journal: Cellular and Molecular Immunology (2022)

Abstract B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders, progress in epigenetic research has revealed new mechanisms leading to B-cell hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate B-cell responses, and their dysregulation can contribute to the pathogenesis of autoimmune diseases. Patients with autoimmune diseases show epigenetic alterations that lead to the initiation and perpetuation of autoimmune inflammation. Moreover, many clinical and animal model studies have shown the promising potential of epigenetic therapies for patients. In this review, we present an up-to-date overview of epigenetic mechanisms with a focus on their roles in regulating functional B-cell subsets. Furthermore, we discuss epigenetic dysregulation in B cells and highlight its contribution to the development of autoimmune diseases. Based on clinical and preclinical evidence, we discuss novel epigenetic biomarkers and therapies for patients with autoimmune disorders.
Acquired mutations in BAX confer resistance to BH3-mimetic therapy in acute myeloid leukemia
Authors: Donia M. Moujalled, Fiona C. Brown, Chong Chyn Chua, Michael A. Dengler, Giovanna Pomilio, Natasha S. Anstee, Veronique Litalien, Ella Thompson, Thomas Morley, Sarah MacRaild, Ing S. Tiong, Rhiannon Morris, Karen Dun, Adrian Zordan, Jaynish Shah, Sebastien Banquet, Ensar Halilovic, Erick Morris, Marco J. Herold, Guillaume Lessene, Jerry M. Adams, David C. S. Huang, Andrew W. Roberts, Piers Blombery, Andrew H. Wei
Journal: Blood (2022)

Randomized trials in acute myeloid leukemia (AML) have demonstrated improved survival by the BCL-2 inhibitor venetoclax combined with azacitidine in older patients, and clinical trials are actively exploring the role of venetoclax in combination with intensive chemotherapy in fitter patients with AML. As most patients still develop recurrent disease, improved understanding of relapse mechanisms is needed. We find that 17% of patients relapsing after venetoclax-based therapy for AML have acquired inactivating missense or frameshift/nonsense mutations in the apoptosis effector gene BAX. In contrast, such variants were rare after genotoxic chemotherapy. BAX variants arose within either leukemic or preleukemic compartments, with multiple mutations observed in some patients. In vitro, AML cells with mutated BAX were competitively selected during prolonged exposure to BCL-2 antagonists. In model systems, AML cells rendered deficient for BAX, but not its close relative BAK, displayed resistance to BCL-2 targeting, whereas sensitivity to conventional chemotherapy was variable. Acquired mutations in BAX during venetoclax-based therapy represent a novel mechanism of resistance to BH3-mimetics and a potential barrier to the long-term efficacy of drugs targeting BCL-2 in AML.
2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department
Authors: Michael C. Kontos, James A. de Lemos, Steven B. Deitelzweig, Deborah B. Diercks, M. Odette Gore, Erik P. Hess, Cian P. McCarthy, James K. McCord, Paul I. Musey, Todd C. Villines, Leesa J. Wright
Journal: Journal of the American College of Cardiology (2022)
Treatment-related thoracic soft tissue sarcomas in US breast cancer survivors: a retrospective cohort study
Authors: Lene H S Veiga, Jacqueline B Vo, Rochelle E Curtis, Matthew M Mille, Choonsik Lee, Cody Ramin, Clara Bodelon, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Heather Spencer Feigelson, Gretchen L Gierach, Amy Berrington de Gonzalez
Journal: The Lancet Oncology (2022)
Minimal information for reporting a genomics experiment
Authors: Kostiantyn Dreval, Paul C. Boutros, Ryan D. Morin
Journal: Blood (2022)

Exome and genome sequencing has facilitated the identification of hundreds of genes and other regions that are recurrently mutated in hematologic neoplasms. The data sets from these studies theoretically provide opportunities. Quality differences between data sets can confound secondary analyses. We explore the consequences of these on the conclusions from some recent studies of B-cell lymphomas. We highlight the need for a minimum reporting standard to increase transparency in genomic research.
Underestimated COVID-19 mortality in WHO African region – Authors' reply
Authors: Joseph Waogodo Cabore, Humphrey Karamagi, Hillary Kipchumba Kipruto, Joseph Kyalo Mungatu, James Avoka Asamani, Benson Droti, Regina Titi-Ofei, Aminata Binetou Wahebine Seydi, Solyana Ngusbrhan Kidane, Thierno Balde, Abdou Salam Gueye, Lindiwe Makubalo, Matshidiso R Moeti
Journal: The Lancet Global Health (2022)
The state of health in Indonesia's provinces, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Nafsiah Mboi, Ruri Syailendrawati, Samuel M Ostroff, Iqbal RF Elyazar, Scott D Glenn, Tety Rachmawati, Wahyu Pudji Nugraheni, Pungkas Bahjuri Ali, Laksono Trisnantoro, Qorinah Estiningtyas Sakilah Adnani, Rozana Ika Agustiya, Agung Dwi Laksono, Budi Aji, Luna Amalia, Ansariadi Ansariadi, Ernoiz Antriyandarti, Irfan Ardani, Ratih Ariningrum, Ni Ketut Aryastami, Djunaedi Djunaedi, Ferry Efendi, Nelsensius Klau Fauk, Ghozali Ghozali, Nariyah Handayani, Harapan Harapan, Arief Hargono, Agus DWI Harso, Hartanti Dian Ikawati, Endang Indriasih, Karlina Karlina, Soewarta Kosen, Asep Kusnali, Dian Kusuma, Melyana Lumbantoruan, Merry Lusiana, Santi Martini, Meilinda meilinda, Rofingatul Mubasyiroh, Dede Anwar Musadad, Dina Nur Anggraini Ningrum, Syarifah Nuraini, Ni'matun Nurlaela, Helena Ullyartha Pangaribuan, Indah Pawitaningtyas, Agung Purnomo, Herti Windya Puspasari, Nurul Puspasari, Setyaningrum Rahmawaty, Hasnani Rangkuti, Betty Roosihermiatie, Tita Rosita, Rustika Rustika, Yoseph Leonardo Samodra, Jenny Veronika Samosir, Siswanto Siswanto, Karen Houston Smith, Agus Sudaryanto, Sugianto Sugianto, Suparmi Suparmi, Ni Ketut Susilarini, Ingan Ukur Tarigan, Jansje Henny Vera Ticoalu, Indang Trihandini, Mugi Wahidin, Tati Suryati Warouw, Retno Widyastuti, Ratna DWI Wulandari, Simon I Hay, Christopher J L Murray, Ali H Mokdad
Journal: The Lancet Global Health (2022)
Southeast Asia needs a revolving fund for vaccines
Authors: Fariza Nasreen Seraj Ahmad, Swee Kheng Khor, Jeremy Lim, Susann Roth, Shita Dewi, Francisco Becerra
Journal: The Lancet Global Health (2022)

COVID-19 vaccination programmes have been relatively successful in the Association of Southeast Asian Nations (ASEAN), blunting the worst of the pandemic and increasing overall public understanding of and support for vaccination programmes. To build on these gains, we propose an ASEAN Vaccines Revolving Fund (AVRF) to strengthen long-term vaccine procurement in the ASEAN, starting with COVID-19 vaccines and expanding to other vaccine-preventable diseases.
Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study
Authors: Sheikh Taslim Ali, Yiu Chung Lau, Songwei Shan, Sukhyun Ryu, Zhanwei Du, Lin Wang, Xiao-Ke Xu, Dongxuan Chen, Jiaming Xiong, Jungyeon Tae, Tim K Tsang, Peng Wu, Eric H Y Lau, Benjamin J Cowling
Journal: The Lancet Global Health (2022)
Two circPPFIA1s negatively regulate liver metastasis of colon cancer via miR-155-5p/CDX1 and HuR/RAB36
Authors: Haein Ji, Tae Won Kim, Woo Joo Lee, Seong Dong Jeong, Yong Beom Cho, Hyeon Ho Kim
Journal: Molecular Cancer (2022)

Circular RNAs (circRNAs) play a critical role in colorectal cancer (CRC) progression, including metastasis. However, the detailed molecular mechanism is not fully understood.Differentially expressed circRNAs between primary KM12C and liver metastatic KM12L4 colon cancer cells were identified by microarray. The expression of circRNAs was measured by semi-quantitative (semi-qPCR) and real time-quantitative PCR (RT-qPCR). Metastatic potential including invasive and migratory abilities, and liver metastasis were examined by transwell assays and intrasplenic injection, respectively. CircPPFIA1-associated microRNA (miRNA) and RNA-binding protein (RBP) were screened by an antisense oligonucleotide (ASO) pulldown experiment. The effects of circPPFIA1 on target gene expression were evaluated by RT-qPCR and western blot analyses.By analyzing circRNA microarray data, we identified two anti-metastatic circRNAs generated from PPFIA1 with different length, which named circPPFIA1-L (long) and -S (short). They were significantly downregulated in liver metastatic KM12L4 cells compared to primary KM12C cells. The knockdown of circPPFIA1s in KM12C enhanced metastatic potential and increased liver metastasis. Conversely, overexpression of circPPFIA1s weakened metastatic potential and inhibited liver metastasis. circPPFIA1s were found to function as sponges of oncogenic miR-155-5p and Hu antigen R (HuR) by an ASO pulldown experiment. circPPFIA1s upregulated tumor-suppressing CDX1 expression and conversely downregulated oncogenic RAB36 by decoying miR-155-5p and by sequestering HuR, respectively.Our findings demonstrate that circPPFIA1s inhibit the liver metastasis of CRC via the miR-155-5p/CDX1 and HuR/RAB36 pathways.
Mast cell-T cell axis alters development of colitis-dependent and colitis-independent colorectal tumours: potential for therapeutically targeting via mast cell inhibition
Authors: Juliana Y Sakita, Jefferson Elias-Oliveira, Daniela Carlos, Emerson de Souza Santos, Luciana Yamamoto Almeida, Tathiane M Malta, Mariângela O Brunaldi, Sergio Albuquerque, Cleide Lúcia Araújo Silva, Marcus V Andrade, Vania L D Bonato, Sergio Britto Garcia, Fernando Queiroz Cunha, Guilherme Cesar Martelossi Cebinelli, Ronaldo B Martins, Jason Matthews, Leandro Colli, Francis L Martin, Sergio A Uyemura, Vinicius Kannen
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. Methods We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models. Results Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy. Conclusion Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.
Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: a before-and-after cross-sectional household serosurvey in four districts, 2018–2020
Authors: Manoj V Murhekar, Nivedita Gupta, Alvira Z Hasan, Muthusamy Santhosh Kumar, V Saravana Kumar, Christine Prosperi, Gajanan N Sapkal, Jeromie Wesley Vivian Thangaraj, Ojas Kaduskar, Vaishali Bhatt, Gururaj Rao Deshpande, Ullas Padinjaremattathil Thankappan, Avi Kumar Bansal, Sanjay L Chauhan, Gangandeep Singh Grover, Arun Kumar Jain, Ragini N Kulkarni, Santanu Kumar Sharma, Itta K Chaaithanya, Sanchit Kharwal, Sunil K Mishra, Neha R Salvi, Sandeep Sharma, Nilanju P Sarmah, R Sabarinathan, Augustine Duraiswamy, D Sudha Rani, K Kanagasabai, Abhishek Lachyan, Poonam Gawali, Mitali Kapoor, Arpit Kumar Shrivastava, Saurabh Kumar Chonker, Bipin Tilekar, Babasaheb V Tandale, Mohammad Ahmad, Lucky Sangal, Amy Winter, Sanjay M Mehendale, William J Moss, Kyla Hayford
Journal: The Lancet Global Health (2022)

India did phased measles-rubella supplementary immunisation activities (MR-SIAs; ie, mass-immunisation campaigns) targeting children aged 9 months to less than 15 years. We estimated measles-rubella seroprevalence before and after the MR-SIAs to quantify the effect on population immunity and identify remaining immunity gaps.Between March 9, 2018 and March 19, 2020 we did community-based, cross-sectional serosurveys in four districts in India before and after MR-SIAs. 30 villages or wards were selected within each district, and one census enumeration block from each was selected as the survey cluster. Households were enumerated and 13 children in the younger age group (9 months to <5 years) and 13 children in the older ager group (5 to <15 years) were randomly selected by use of computer-generated random numbers. Serum samples were tested for IgG antibodies to measles and rubella viruses by enzyme immunoassay.Specimens were collected from 2570 children before the MR-SIA and from 2619 children afterwards. The weighted MR-SIA coverage ranged from 73·7% to 90·5% in younger children and from 73·6% to 93·6% in older children. Before the MR-SIA, district-level measles seroprevalence was between 80·7% and 88·5% among younger children in all districts, and between 63·4% and 84·5% among older children. After the MR-SIA, measles seroprevalence among younger children increased to more than 90% (range 91·5 to 96·0) in all districts except Kanpur Nagar, in which it remained unchanged 80·4%. Among older children, measles seroprevalence increased to more than 90·0% (range 93·7% to 96·5%) in all districts except Hoshiarpur (88·7%). A significant increase in rubella seroprevalence was observed in all districts in both age groups, with the largest effect in Dibrugarh, where rubella seroprevalence increased from 10·6% to 96·5% among younger children.Measles-rubella seroprevalence increased substantially after the MR-SIAs but the serosurvey also identified remaining gaps in population immunity.The Bill & Melinda Gates Foundation and Indian Council of Medical Research.
Evaluating and mitigating the potential indirect effect of COVID-19 on control programmes for seven neglected tropical diseases: a modelling study
Authors: Anna Borlase, Epke A Le Rutte, Soledad Castaño, David J Blok, Jaspreet Toor, Federica Giardina, Emma L Davis, Maryam Aliee, Roy M Anderson, Diepreye Ayabina, Maria-Gloria Basáñez, Seth Blumberg, Rocio M Caja Rivera, Nakul Chitnis, Luc E Coffeng, Christopher N Davis, Michael Deiner, Peter J Diggle, Claudio Fronterrè, Emanuele Giorgi, Matthew Graham, Jonathan ID Hamley, T Deirdre Hollingsworth, Matt J Keeling, Klodeta Kura, Thomas M Lietman, Veronica Malizia, Graham F Medley, Edwin Michael, S Mwangi Thumbi, Nyamai Mutono, Travis Porco, Joaquín M Prada, Kat S Rock, Swarnali Sharma, Simon Spencer, Wilma A Stolk, Panayiota Touloupou, Andreia Vasconcelos, Carolin Vegvari, Sake J de Vlas
Journal: The Lancet Global Health (2022)
Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field
Authors: Yucong Li, Linlong Li, Ye Li, Lu Feng, Bin Wang, Ming Wang, Haixing Wang, Meiling Zhu, Yongkang Yang, Erik I. Waldorff, Nianli Zhang, Ingmar Viohl, Sien Lin, Liming Bian, Wayne Yuk-Wai Lee, Gang Li
Journal: Bioactive Materials (2022)

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.
Women's risk of death beyond 42 days post partum: a pooled analysis of longitudinal Health and Demographic Surveillance System data in sub-Saharan Africa
Authors: Ursula Gazeley, Georges Reniers, Hallie Eilerts-Spinelli, Julio Romero Prieto, Momodou Jasseh, Sammy Khagayi, Veronique Filippi
Journal: The Lancet Global Health (2022)
Re-evaluating the health impact and cost-effectiveness of tuberculosis preventive treatment for modern HIV cohorts on antiretroviral therapy: a modelling analysis using data from Tanzania
Authors: Jinyi Zhu, Goodluck Lyatuu, Christopher R Sudfeld, Anna Kiravu, David Sando, Lameck Machumi, John Minde, Fikiri Chisonjela, Ted Cohen, Nicolas A Menzies
Journal: The Lancet Global Health (2022)